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1.
Front Oncol ; 14: 1426002, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978730

RESUMO

Objectives: To assess the comparative efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S) versus concurrent chemoradiotherapy (CCRT) for patients with cervical cancer stages IB2 to IIB. Method: An exhaustive literature search was conducted up to November 2023 in databases including PubMed, Embase, Web of Science, and the Cochrane Library, focusing on disease-free survival (DFS) and overall survival (OS). Data were analyzed using STATA version 15. Results: The meta-analysis included data from two randomized controlled trials and eight retrospective cohort studies, totaling 2,879 patients with stages IB2 to IIB cervical cancer. Pooled data showed no significant difference in OS [hazard ratio (HR) 0.71, 95% confidence interval (CI): 0.51 to 1.00, p = 0.052] and DFS (HR 0.65, 95% CI: 0.38 to 1.14, p = 0.132) between NACT+S and CCRT. Subgroup analysis revealed that NACT+S provided a better OS in Asian populations, retrospective cohort studies, TP regimen chemotherapy, and multivariate analysis. Conclusion: The findings indicate that CCRT and NACT+S are comparably effective for treating cervical cancer stages IB2 to IIB. Notably, in specific subgroups such as Asian patients and those receiving the TP regimen, NACT+S appears to enhance OS.

2.
Arch Dermatol Res ; 316(7): 468, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39002062

RESUMO

Epidermal Growth Factor Receptor Inhibitors (EGFRIs) is a common cancer therapy, but they occasionally cause severe side effects such as xerosis. Tiansha mixture (TM), a traditional Chinese medicines formulation, is develpoed to treat xerosis. This study aims to understand mechanisms of TM on xerosis. Bio-active compounds were selected from databases (TCMSP, TCM-ID, HERB, ETCM) and removed for poor oral bioavailability and low drug likeness. Then a network-based approach filtered out potential active compounds against xerosis. KEGG enrichment analysis identified PI3K/AKT and ERK/MAPK pathways, which were further verified by molecular docking. Afterwards, the effect of TM on activation of PI3K/AKT and ERK/MAPK pathways was validated in gefitinib-induced xerosis rats, where AKT-activator SC79 and MAPK-activator CrPic were also applied. Skin damage was assessed by dorsal score and HE and Tunel stainings. the levels of inflammation factors IL-6 and TNF-α in serum and skin tissue were measured by ELISA. Western blot was used to detect protein levels in the pathways. Network pharmacology identified 111 bio-active compounds from TM and 14 potential targets. Docking simulation showed apigenin, luteolin, and quercetin bio-active compounds in TM bound to IKBKG, INSR, and RAF-1 proteins. In xerosis model rats, TM mitigated xerosis damage, decreased inflammation factors, and phosphorylation of PI3K/AKT and ERK/MAPK proteins. SC79 or CrPic or their combination reversed TM's effect. The current study identified potential targets and PI3K/AKT and ERK/MAPK pathways involved in the effect of TM on xerosis, thus providing a foundation for TM clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Animais , Farmacologia em Rede/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Ratos , Modelos Animais de Doenças , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Masculino , Pele/efeitos dos fármacos , Pele/patologia , Transdução de Sinais/efeitos dos fármacos , Ratos Sprague-Dawley , Fosfatidilinositol 3-Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Interleucina-6/metabolismo
3.
Nutrients ; 16(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38999767

RESUMO

(1) Background: The benefits of weight management are widely recognized, and prolonged fasting duration has become a common method for weight control. The suitability of time-restricted eating (TRE) for elderly individuals remains controversial. This study aims to examine the correlation between fasting duration and mortality within a nationally representative cohort of elderly individuals in the United States. (2) Methods: Data were extracted from a prospective cohort study conducted as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Participants aged over 60 with complete data on dietary intake and mortality follow-up information were included. Fasting duration was assessed using two 24 h dietary recalls. All the participants were categorized into fasting duration quartiles. Mortality outcomes were ascertained through the National Death Index. Cox proportional hazards regression models were utilized to analyze the association between fasting duration and mortality. (3) Results: The final analysis included 10,561 elderly participants (mean age 69.89, 45.58% male). Individuals with the longest fasting duration (over 12.38 h) had a significantly higher risk of CVD mortality compared to those with a normal fasting duration (10.58-12.38 h). This elevated CVD mortality risk was particularly pronounced in males, individuals over 70 years old, and non-shift workers. A non-linear relationship was observed between fasting duration and all-cause mortality and CVD mortality. (4) Conclusions: Prolonged fasting periods are associated with a higher risk of CVD mortality in the elderly population, although this correlation is not evident for all-cause, cancer, or other-cause mortality. A fasting duration of 11.49 h correlates with the lowest mortality risk. Additionally, elderly individuals with the shortest fasting duration exhibit elevated hazard ratios for both cancer and other-cause mortality. As with any health intervention, clinicians should exercise caution when recommending a fasting regimen that is personalized to the health condition of people who are older. Further research through randomized controlled trials should be conducted to comprehensively investigate the impact of TRE on mortality.


Assuntos
Jejum , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Idoso , Estudos Prospectivos , Estados Unidos/epidemiologia , Fatores de Tempo , Doenças Cardiovasculares/mortalidade , Fatores de Risco , Modelos de Riscos Proporcionais , Pessoa de Meia-Idade , Mortalidade , Idoso de 80 Anos ou mais , Causas de Morte
4.
Exp Biol Med (Maywood) ; 249: 10051, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881848

RESUMO

Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.


Assuntos
Dioxigenases , Diterpenos , Compostos de Epóxi , Fenantrenos , Podócitos , Proteína da Zônula de Oclusão-1 , Podócitos/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/patologia , Proteína da Zônula de Oclusão-1/metabolismo , Fenantrenos/farmacologia , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Dioxigenases/metabolismo , Animais , Proteínas de Ligação a DNA/metabolismo , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Permeabilidade/efeitos dos fármacos , Humanos , Metilação de DNA/efeitos dos fármacos
5.
Pestic Biochem Physiol ; 202: 105951, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879336

RESUMO

The abuse of chemical insecticides has led to strong resistance in cockroaches, and biopesticides with active ingredients based on insect pathogens have good development prospects; however, their slow effect has limited their practical application, and improving their effectiveness has become an urgent problem. In this study, the interaction between Serratia marcescens and Metarhizium anisopliae enhanced their virulence against Blattella germanica and exhibited a synergistic effect. The combination of S. marcescens and M. anisopliae caused more severe tissue damage and accelerated the proliferation of the insect pathogen. The results of high-throughput sequencing demonstrated that the gut microbiota was dysbiotic, the abundance of the opportunistic pathogen Weissella cibaria increased, and entry into the hemocoel accelerated the death of the German cockroaches. In addition, the combination of these two agents strongly downregulated the expression of Imd and Akirin in the IMD pathway and ultimately inhibited the expression of antimicrobial peptides (AMPs). S. marcescens released prodigiosin to disrupted the gut homeostasis and structure, M. anisopliae released destruxin to damaged crucial organs, opportunistic pathogen Weissella cibaria overproliferated, broke the gut epithelium and entered the hemocoel, leading to the death of pests. These findings will allow us to optimize the use of insect pathogens for the management of pests and produce more effective biopesticides.


Assuntos
Baratas , Microbioma Gastrointestinal , Metarhizium , Serratia marcescens , Animais , Serratia marcescens/patogenicidade , Serratia marcescens/fisiologia , Metarhizium/patogenicidade , Metarhizium/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Baratas/microbiologia , Prodigiosina/farmacologia , Micotoxinas/metabolismo , Blattellidae/microbiologia , Controle Biológico de Vetores/métodos , Virulência , Depsipeptídeos
6.
Cancer Sci ; 115(7): 2235-2253, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38700108

RESUMO

Triple-negative breast cancer (TNBC) has greater infiltration of M2-like macrophages (TAMs), which enhances cancer cell invasion and leads to a poor prognosis. TNBC progression is mediated by both tumor cells and the tumor microenvironment (TME). Here we elucidate the mechanism of the interaction between TNBC cells and TAMs. In this study, we confirmed that CD44v5 is highly expressed in TNBC, which drives TNBC cell metastasis and promotes TAM polarization by co-localizing with IL4Rα and inhibiting its internalization and degradation, thereby promoting activation of the STAT3/IL6 signaling axis. At the same time, TAMs also facilitate TNBC cell metastasis by secreting IL-4, IL-6, and other cytokines, in which the IL-4/IL-4R/STAT3/IL-6 signaling axis plays the same role for TNBC cells responding to TAMs. Moreover, we found that the above progress could be suppressed when the CD44v5 domain was blocked. We demonstrated that the CD44v5/IL-4R/STAT3/IL-6 signaling pathway plays a key role in TNBC cell metastasis, and in TNBC cells inducing TAM polarization and responding to TAMs, promoting metastasis. Collectively, we suggest that the CD44v5 domain may be a promising target for regulating the TME of TNBC as well as treating TNBC.


Assuntos
Receptores de Hialuronatos , Fator de Transcrição STAT3 , Transdução de Sinais , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Receptores de Hialuronatos/metabolismo , Feminino , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Linhagem Celular Tumoral , Animais , Camundongos , Interleucina-6/metabolismo , Subunidade alfa de Receptor de Interleucina-4/metabolismo , Subunidade alfa de Receptor de Interleucina-4/genética , Interleucina-4/metabolismo
7.
J Cell Mol Med ; 28(9): e18374, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722288

RESUMO

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.


Assuntos
Neoplasias da Mama , Organoides , Medicina de Precisão , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Organoides/efeitos dos fármacos , Organoides/patologia , Organoides/metabolismo , Medicina de Precisão/métodos , Animais , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Pessoa de Meia-Idade
9.
Shock ; 62(1): 139-145, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38546380

RESUMO

ABSTRACT: Introduction: Intestinal flora and the translocation of its products, such as muramyl dipeptide (MDP), are common causes of sepsis. MDP is a common activator of the intracellular pattern recognition receptor NOD2, and MDP translocation can cause inflammatory damage to the small intestine and systemic inflammatory responses in rats. Therefore, this study investigated the effects of MDP on the intestinal mucosa and distant organs during sepsis and the role of the NOD2/AMPK/LC3 pathway in MDP-induced mitochondrial dysfunction in the intestinal epithelium. Methods: Fifty male Sprague Dawley rats were randomly divided into five treatment groups: lipopolysaccharide (LPS) only, 1.5 and 15 mg/kg MDP+LPS, and 1.5 and 15 mg/kg MDP+short-peptide enteral nutrition (SPEN)+LPS. The total caloric intake was the same per group. The rats were euthanized 24 h after establishing the model, and peripheral blood and small intestinal mucosal and lung tissues were collected. Results: Compared to the LPS group, both MDP+LPS groups had aggravated inflammatory damage to the intestinal mucosal and lung tissues, increased IL-6 and MDP production, increased NOD2 expression, decreased AMPK and LC3 expression, increased mitochondrial reactive oxygen species production, and decreased mitochondrial membrane potential. Compared to the MDP+LPS groups, the MDP+SPEN+LPS groups had decreased IL-6 and MDP production, increased AMPK and LC3 protein expression, and protected mitochondrial and organ functions. Conclusions: MDP translocation reduced mitochondrial autophagy by regulating the NOD2/AMPK/LC3 pathway, causing mitochondrial dysfunction. SPEN protected against MDP-induced impairment of intestinal epithelial mitochondrial function during sepsis.


Assuntos
Acetilmuramil-Alanil-Isoglutamina , Mucosa Intestinal , Mitocôndrias , Proteína Adaptadora de Sinalização NOD2 , Ratos Sprague-Dawley , Animais , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Masculino , Ratos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteína Adaptadora de Sinalização NOD2/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Citocinas/metabolismo , Lipopolissacarídeos/toxicidade , Sepse/metabolismo , Interleucina-6/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Inflamação/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
Open Life Sci ; 19(1): 20220824, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465339

RESUMO

Trousseau syndrome (TS) is a malignant tumor-mediated complication of the hypercoagulable state with an unknown etiology. Laboratory testing results in patients with TS have indicated elevated D-dimer levels. The imaging analysis in patients who had undergone stroke has shown the presence of several cerebral infarction lesions in multiple regions. Since patients have had malignant tumors for a long time when they suffer from a secondary stroke, the optimum time for radical tumor treatment is usually missed. This study reports a case to improve the early screening and detection of TS and reduce the risk of recurrence of cerebral infarction.

11.
J Hazard Mater ; 469: 133862, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38432090

RESUMO

The precise mechanism behind the association between plants' reactions to cadmium (Cd) stress and brassinosteroid (BR) remains unclear. In the current investigation, Cd stress quickly increased the endogenous BR concentration in the rice roots. Exogenous BR also increased the hemicellulose level in the root cell wall, which in turn increased its capacity to bind Cd. Simultaneously, the transcription level of genes responsible for root Cd absorption was decreased, including Natural Resistance-Associated Macrophage Protein 1/5 (OsNRAMP1/5) and a major facilitator superfamily gene called OsCd1. Ultimately, the increased expression of Heavy Metal ATPase 3 (OsHMA3) and the decreased expression of OsHMA2, which was in charge of separating Cd into vacuoles and translocating Cd to the shoots, respectively, led to a decrease in the amount of Cd that accumulated in the rice shoots. In contrast, transgenic rice lines overexpressing OsGSK2 (a negative regulator in BR signaling) accumulated more Cd, while OsGSK2 RNA interference (RNAi) rice line accumulated less Cd. Furthermore, BR increased endogenous Gibberellic acid (GA) level, and applying GA could replicate its alleviative effect. Taken together, BR decreased Cd accumulation in rice by mediating the cell wall's fixation capacity to Cd, which might relied on the buildup of the GA.


Assuntos
Cádmio , Giberelinas , Oryza , Cádmio/metabolismo , Oryza/genética , Oryza/metabolismo , Brassinosteroides , Parede Celular/metabolismo , Raízes de Plantas/metabolismo
12.
Transl Oncol ; 43: 101921, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38402722

RESUMO

BACKGROUND: Lung adenocarcinoma is the most common source of brain metastasis (BM), resulting in significant morbidity and mortality. We aimed to identify patients with high BM risk who possibly benefit from brain-penetrant drugs, prophylactic cranial irradiation, or close brain magnetic resonance imaging surveillance. METHODS: Metastatic lung adenocarcinoma patients with extracranial tumor samples profiled by a next-generation sequencing panel targeting 425 tumor-related genes were retrospectively enrolled between February 2008 and July 2021. We compared BM and non-BM patients' genomic and clinical features and studied their associations with BM risk. Two external cohorts were used for result validation and molecular mechanisms investigation, respectively. RESULTS: We included 174 eligible patients, including 90 having developed BM by the end of follow-up. Age≤60, EGFR activating mutations, and high-level apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) mutational signatures were associated with elevated BM risk. Similar findings in BM-free survival were obtained by fitting Fine-Gray subdistribution hazard models addressing competing risks. Increased BM risk related to APOBEC mutational signatures was validated in an external cohort (N = 440). RNA sequencing data analyses performed in another external cohort (N = 230) revealed that expressions of metastasis-related pathways such as transforming growth factor (TGF)ß and epithelial-mesenchymal transition (EMT) were upregulated in the patients with high-level APOBEC mutational signatures. CONCLUSION: APOBEC mutational signatures related to upregulated TGFß and EMT, could serve as an independent risk factor for BM and BM-free survival in metastatic lung adenocarcinoma patients. Further investigations are warranted to tailor personalized treatments to improve the susceptible patient's outcomes.

13.
Neoplasia ; 50: 100979, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38387107

RESUMO

BACKGROUND: Despite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. [3] Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. [4-6] There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy. METHODS: We retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3. FINDINGS: A total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001). INTERPRETATION: IASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Quimioterapia Adjuvante , Estadiamento de Neoplasias , Prognóstico
14.
Open Forum Infect Dis ; 11(2): ofad649, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38312215

RESUMO

Background: Due to scarce therapeutic options, hospital-acquired infections caused by Klebsiella pneumoniae (KP), particularly carbapenem-resistant KP (CRKP), pose enormous threat to patients' health worldwide. This study aimed to characterize the epidemiology and risk factors of CRKP among nosocomial KP infections. Method: MEDLINE, Embase, PubMed, and Google Scholar were searched for studies reporting CRKP prevalence from inception to 30 March 2023. Data from eligible publications were extracted and subjected to meta-analysis to obtain global, regional, and country-specific estimates. To determine the cause of heterogeneity among the selected studies, prespecified subgroup analyses and meta-regression were also performed. Odds ratios of CRKP-associated risk factors were pooled by a DerSimonian and Laird random-effects method. Results: We retained 61 articles across 14 countries and territories. The global prevalence of CRKP among patients with KP infections was 28.69% (95% CI, 26.53%-30.86%). South Asia had the highest CRKP prevalence at 66.04% (95% CI, 54.22%-77.85%), while high-income North America had the lowest prevalence at 14.29% (95% CI, 6.50%-22.0%). In the country/territory level, Greece had the highest prevalence at 70.61% (95% CI, 56.77%-84.45%), followed by India at 67.62% (95% CI, 53.74%-81.79%) and Taiwan at 67.54% (95% CI, 58.65%-76.14%). Hospital-acquired CRKP infections were associated with the following factors: hematologic malignancies, corticosteroid therapies, intensive care unit stays, mechanical ventilations, central venous catheter implantations, previous hospitalization, and antibiotic-related exposures (antifungals, carbapenems, quinolones, and cephalosporins). Conclusions: Study findings highlight the importance of routine surveillance to control carbapenem resistance and suggest that patients with nosocomial KP infection have a very high prevalence of CRKP.

15.
In Vitro Cell Dev Biol Anim ; 60(1): 54-66, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38123756

RESUMO

Postmenopausal osteoporosis (PMOP) is a common disease that endangers the health of elderly women. Cucumber seeds have shown excellent therapeutic effects on PMOP, but the mechanism of cucumber seed peptide (CSP) remains unclear. The expression levels of NF-κB and osteoclast-related genes were detected by RT-qPCR. The levels of apoptosis-related proteins were detected by Western blotting. Nuclear translocation of NF-κB p65 and osteoclast formation were detected by immunofluorescence and tartrate-resistant acid phosphatase (TRAP) staining, respectively. ELISA was used to detect the expression levels of OPG, M-CSF, and RANKL. Hematoxylin-eosin (H&E) and TRAP staining were used to observe the effects of CSP on bone formation. In RAW264.7 cells, CSP (0.4 mg/L, 4 mg/L, and 40 mg/L) effectively inhibited the expression of osteoclast-related genes (Cathepsin-K, MT1-MMP, MMP-9, and TRAP). TRAP-positive multinucleated giant cells gradually decreased. Furthermore, NF-κB pathway activation downstream of RANK was inhibited. In bone marrow stromal cells (BMSCs), the expression levels of M-CSF and RANKL gradually decreased, and OPG gradually increased with increasing CSP concentrations. Treatment of RAW264.7 cells with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) prevented the formation of osteoclasts. Treatment with different concentrations of CSP effectively decreased the levels of RANKL and M-CSF in rat serum and increased the expression of OPG in the oophorectomy (OVX) rat model. Furthermore, different concentrations of CSP could ameliorate the loss of bone structure and inhibit the formation of osteoclasts in rats. CSP inhibits osteoclastogenesis by regulating the OPG/RANKL/RANK pathway and inhibiting the NF-kB pathway.


Assuntos
Cucumis sativus , NF-kappa B , Animais , Feminino , Humanos , Ratos , Diferenciação Celular , Cucumis sativus/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Osteogênese , Ligante RANK/metabolismo , Camundongos
16.
World J Gastroenterol ; 29(39): 5435-5451, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37900996

RESUMO

Small extracellular vesicles (exosomes) are important components of the tumor microenvironment. They are small membrane-bound vesicles derived from almost all cell types and play an important role in intercellular communication. Exosomes transmit biological molecules obtained from parent cells, such as proteins, lipids, and nucleic acids, and are involved in cancer development. MicroRNAs (miRNAs), the most abundant contents in exosomes, are selectively packaged into exosomes to carry out their biological functions. Recent studies have revealed that exosome-delivered miRNAs play crucial roles in the tumorigenesis, progression, and drug resistance of hepatocellular carcinoma (HCC). In addition, exosomes have great industrial prospects in the diagnosis, treatment, and prognosis of patients with HCC. This review summarized the composition and function of exosomal miRNAs of different cell origins in HCC and highlighted the association between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC. Finally, we described the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Exossomos , Vesículas Extracelulares , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Exossomos/genética , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Microambiente Tumoral/genética
17.
Materials (Basel) ; 16(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37834650

RESUMO

Gas protection is a crucial part of quality control in laser welding, especially for titanium alloy, which oxidizes easily at high temperatures. Substantial experiments concerning shielding gas characteristics in the welding process have been implemented. However, the common analysis conducted is simplistic and lacks a theoretical basis. This paper presented an investigation of the shielding gas behaviors based on numerical simulation and a titanium alloy laser welding experiment. The numerical model was established and validated by experiment. Subsequently, the temperature field and gas flow fields were calculated. By combining the two fields, the threshold temperature of gas protection was determined, and the influence of shielding gas parameters on the protection effect was examined. The results revealed that the protection of the high-temperature zone was primarily influenced by the nozzle height, nozzle inner diameter, and nozzle angle, while the plasma suppression effect was mainly correlated with the nozzle inner diameter and gas flow rate. These initial findings provide scientific guidance for the better quality production of laser beam welded components made of not only titanium alloy but also other metallic materials.

18.
BMC Oral Health ; 23(1): 672, 2023 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-37718438

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is more common in men aged 40 to 59, and radiotherapy is an effective treatment. Nasopharyngeal lymphoma (NPL) is rare, and the coexistence of nasopharyngeal mantle cell lymphoma (MCL) and NPC is even rarer. A collision tumor is a rare type of tumor that refers to two or more different tumors occurring in the same organ. No reports to date have described a collision tumor of NPC and MCL occurring within the same nasopharyngeal mass. We herein report the successful treatment of a unique case of synchronous coexistence of NPC and MCL occurring in the nasopharynx of a Chinese man. CASE PRESENTATION: A 58-year-old man presented with a 5-month history of swallowing discomfort. Biopsy was performed under nasopharyngeal endoscopy, and histopathology revealed NPC. Magnetic resonance imaging revealed lesions in the nasopharynx, oropharynx, and tonsils, as well as enlarged lymph nodes in the parotid gland, posterior ear, and neck. This may be a synchronous dual primary tumor coexisting with NPC and NPL. Pathology consultation confirmed that the biopsy specimen of the nasopharynx was a collision tumor of NPC and MCL. Positron emission tomography computed tomography (PET-CT) revealed thickening of the posterior wall of the nasopharynx, which was considered NPC with lymphoma. The enlargement of the pharyngeal lymph ring and multiple hypermetabolic lymph nodes were evaluated as lymphoma infiltration. The patient received two courses of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by head and neck radiotherapy. At the time of this writing, he had remained alive without recurrence for 61 months since the initial treatment and was still undergoing follow-up. CONCLUSIONS: It is very important to correctly recognize collision tumors. Magnetic resonance imaging helps identify different components of collision tumors. Pathological examination helps to confirm the diagnosis. Histological examination reveals different components, and PET-CT can help determine the extent of the lesion. Dose-adjusted chemotherapy combined with radiotherapy may have promising herapeutic effects, but additional case studies are needed to confirm.


Assuntos
Linfoma de Célula do Manto , Neoplasias Nasofaríngeas , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Linfoma de Célula do Manto/diagnóstico por imagem , Linfoma de Célula do Manto/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Nasofaríngeas/diagnóstico por imagem , Nasofaringe
19.
Vet Med Sci ; 9(6): 2617-2624, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37723902

RESUMO

Mycobacterium phlei is a gram-positive acid-fast mycobacterium from the family Mycobacteriaceae. It is a valuable resource for both natural drugs and microecological preparations. It has been widely used in the field of human medicine; however, in the field of animal husbandry and veterinary medicine, the research and application of M. phlei is still in the preliminary exploration stage. This study aims to summarize the research progress of M. phlei in the field of veterinary medicine and provide a valuable reference for future research. Key words, such as 'M. phlei', 'veterinary field', 'immune balancer', 'genome' and other relevant words to this study, were used to search through PubMed, Web of Science, SciELO, Science Direct and Google Scholar databases. The results showed that the culture conditions of M. phlei were relatively simple, but its bacterial composition and genome sequence were relatively complex, and various components in the cell wall may have immunoregulatory effects. Therefore, the inactivated preparation made from M. phlei can have various applications in the veterinary field, such as growth regulation, immune regulation, antitumour, anti-parasite and asthma treatment. The literature review indicates that M. phlei preparation is an efficient and convenient immune system balance agent. Despite the challenges associated with the use of M. phlei preparations, it has a strong potential for application in veterinary medicine.


Assuntos
Asma , Mycobacterium , Humanos , Animais , Mycobacterium phlei/genética , Asma/veterinária , Parede Celular
20.
World J Clin Cases ; 11(26): 6289-6297, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37731579

RESUMO

BACKGROUND: Collision tumors of primary malignant lymphoma and adenocarcinoma in the colon are rare. Primary diffuse large B-cell lymphoma (DLBCL)-adenocarcinoma collision tumors are especially rare. CASE SUMMARY: A 74-year-old woman presented with abdominal pain of 1 mo duration. Biopsy under colonoscopy revealed adenocarcinoma of the ascending colon. Subsequently, the patient underwent laparoscopic radical resection of right colon cancer with lymph node dissection. A collision tumor was found incidentally through postoperative pathological sampling. Genetic analysis showed a collision tumor of DLBCL with germinal center B-cell subtype and TP53 mutation, and adenocarcinoma arising in a tubulovillous adenoma in the colon, with BRAF mutation and mutL homolog 1 promoter methylation. The patient died 3 mo after surgery. To our knowledge, this is the 23rd reported case of collision tumor of colorectal adenocarcinoma and lymphoma. The mean age of the 23 patients was 73 years. The most common site was the cecum. There were 15 cases with follow-up data including 11 living and four dead with a 3-year overall survival rate of 71.5%. CONCLUSION: Based on pathological and genetic analysis, surgery combined with chemotherapy or chemoradiotherapy may have good therapeutic effects for collision tumor.

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